Metabolic enzymes such as proteases or kinases are enzymes that are widely distributed in the animal kingdom. Non-exhaustive examples that may be mentioned, as bibliographic references for the proteases, include documents: “Methods in Enzymology XLII (1975)” and “Journal of Medicinal Chemistry” Vol. 43, No. 3 (D. Leung, G. Abbenante and D. P. Fairlie), and, for the kinases, include document: “Methods in Enzymology”, Vol. 80 (1981) (Academic Press Inc.).
Among the proteases capable of selectively catalyzing the hydrolysis of polypeptide bonds, mention may be made of the four main classes: aspartic protease, serine protease, cysteine protease and metalloprotease.
Aspartic proteases that may especially be mentioned include HIV-1 protease, renin, plasmepsins and cathepsin D.
Serine proteases that may especially be mentioned include thrombin, factor Xa, elastase, tryptase, “convertase complement” and hepatitis C protease NS3.
Among the cysteine proteases, there are three structurally different groups, the papain and cathepsin group, the ICE group (caspases) and the picorna-viral group (similar to the serine proteases, in which the serine is replaced with a cysteine).
Thus, mention may be made especially of cathepsin K, cathepsin B, cathepsin L, cathepsin S, caspases, rhinovirus 3C protease and papains and calpains.
Metalloprotease is that may especially be mentioned include angiotensin conversion enzyme, neutral endopeptidase and a mixture of the two, matrix metalloprotease and also tumor necrosis factor-α-converting enzyme.
These kinases or proteases are involved in catabolization and inter- and intracellular communication processes: they play an important role in a large number of diseases in various fields, such as, especially, the cardiovascular field, oncology, the central nervous system, inflammation, osteoporosis, and also parasitic, fungal or viral infectious diseases. Consequently, these proteins are targets of great interest for pharmaceutical research.